ARTICLE
Underlying Causes of Recurrent Pneumonia
in Children
Abdullah F. Owayed, MD; Douglas M. Campbell, MD; Elaine E. L. Wang, MD, FRCPC
Objectives: To determine the relative frequency of un-
derlying factors for recurrent pneumonia and the proportion of patients in whom the underlying illness diagnosis was known prior to pneumonia recurrence.
Methods: Retrospective medical record review for a 10year period from January 1987 through December 1997
at The Hospital for Sick Children in Toronto, Ontario, a
tertiary care pediatric hospital. Recurrent pneumonia was
defined as at least 2 pneumonia episodes in a 1-year period or at least 3 during a lifetime.
Results: Of 2952 children hospitalized with pneumonia, 238 (8%) met criteria for recurrent pneumonia. An
underlying illness diagnosis was identified in 220 (92%).
Of these, the underlying illness was diagnosed prior to
pneumonia in 178 (81%), with the first episode in 25
(11%), and during recurrence in 17 (8%). Underlying illnesses included oropharyngeal incoordination with as-
piration syndrome (114 cases [48%]), immune disorder
(24 [10%]), congenital cardiac defects (22 [9%]), asthma
(19 [8%]), pulmonary anomalies (18 [8%]), gastroesophageal reflux (13 [5%]), and sickle cell anemia (10
[4%]). Clinical clues to diagnosis were recurrent infections at other locations and failure to thrive in the cases
of an immune disorder, recurrences involving the same
location in those with underlying pulmonary pathology, the association of respiratory symptoms with feeding in those with gastroesophageal reflux, or recurrent
wheezing in asthmatic children.
Conclusions: Recurrent pneumonia occurs in fewer than
one tenth of all children hospitalized with pneumonia.
Most of them have a known predisposing factor. The most
common cause was oropharyngeal incoordination.
Arch Pediatr Adolesc Med. 2000;154:190-194
Editor’s Note: This neat, simple study provides valuable infor-
mation that should allow us to breathe easier regarding unwanted
surprises in the case of children with recurrent pneumonia.
Catherine D. DeAngelis, MD
P
From the Department of
Pediatrics, University of
Toronto, and The Hospital
for Sick Children,
Toronto, Ontario.
NEUMONIA IS a major problem in children, especially
those younger than 5 years,
accounting for up to 5 million deaths each year in developing countries.1-4 In North America,
the annual incidence of pneumonia ranges
from 30 to 45 cases per 1000 children in
those younger than 5 years to 16 to 22
cases per 1000 children in those aged 5
years and older.5,6 A subgroup of these children suffer from recurrent pneumonia,
raising the question of whether there is an
underlying illness predisposing them to
such pneumonia recurrences.
Recurrent pneumonia has been defined as at least 2 pneumonia episodes in
1 year or more than 3 at any time, with
radiographic clearing between episodes.7
ARCH PEDIATR ADOLESC MED/ VOL 154, FEB 2000
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Although several review articles7-11 describe possible approaches to investigations for recurrent pneumonia, there are
surprisingly few primary studies of such
children. These previous series may not be
generalizable to most recurrent pneumonia patients cared for in our setting because they have consisted of immunocompromised populations,12-14 were limited to
cases of bacterial pneumonia,15-17 or were
not performed in an industrialized country.18 The purpose of this study is to describe the underlying illnesses of children with recurrent pneumonia hospitalized
in a tertiary care pediatric hospital. From
these data, a series of investigations for
the child with recurrent pneumonia is
proposed.
RESULTS
Two thousand nine hundred fifty-two patients were admitted to the hospital with
pneumonia during a 10-year span; 238
(8%) met the definition for recurrent pneumonia. Of these, 139 (58.4%) were male.
The mean age when recurrent pneumo-
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PATIENTS AND METHODS
A medical record review was performed on all children with
recurrent pneumonia. All children admitted to The Hospital for Sick Children, Toronto, Ontario, from January 1987
through December 1997 with a hospital discharge diagnosis of pneumonia were identified. The hospital is a tertiary
care referral center but also serves as the pediatric hospital for children in downtown Toronto. Children younger
than 18 years are admitted to the hospital. The records of
all children with diagnostic codes corresponding to a diagnosis of pneumonia were identified according to the International Classification of Diseases, Ninth Revision, Clinical Modification19 (codes 480-487, 507). Patients were
included in this analysis if they had 2 or more episodes of
pneumonia per year or 3 or more episodes in a lifetime and
if there was radiographic confirmation of pneumonia during hospital admission. Only patients with pneumonia who
were hospitalized or whose diagnosis was recorded on
admission to our hospital would be identified.
Patients were classified according to underlying illnesses that have previously been associated with childhood pneumonia.7-11 These include oromotor incoordination and swallowing dysfunction predisposing to aspiration
syndrome20-22; immune disorders, including primary and
acquired immunodeficiency syndrome13,14; underlying congenital heart defects23,24; underlying lung and airway problems, such as bronchial asthma25,26; and gastroesophageal
reflux.27,28 Using a standardized data extraction form, information was obtained on patient demographic characteristics, including date of birth, sex, age at diagnosis,
nia was diagnosed was 3.7 years (age range, 2.5 months15.6 years).
An underlying illness was identified in 220 (92.4%)
of the patients (Table 1). One hundred fourteen patients (47.9%) had an underlying aspiration syndrome
secondary to oropharyngeal muscular incoordination leading to an inability to handle respiratory tract secretions.
Twenty-four patients (10.1%) had immune disorders; 22
(9.2%) had congenital heart disease; 19 (7.9%) had bronchial asthma; 18 (7.6%) had congenital or acquired
anomalies of the airways or lungs; 13 (5.4%) had gastroesophageal reflux; 10 (4.2%) had sickle cell anemia;
and no predisposing factors could be identified in the remaining 18 (7.6%).
All patients with aspiration disorders had involvement on radiography of more than one lung lobe. Of these,
cerebral palsy accounted for nearly half the causes. The
mean age at diagnosis of recurrent pneumonia in children with aspiration disorders was 6.3 years. Of the 24
patients who had immune disorders, 13 had malignant
neoplasms; 5, dysgammaglobulinemia (3, hypogammaglobulinemia; 1, hyperimmunoglobulin E syndrome; 1,
agammaglobulinemia); 5, HIV infection; and 1, autoimmune pancytopenia. The mean age at diagnosis of recurrent pneumonia in children with immune disorders was
3.8 years.
The patients with congenital heart disease
included 16 (72.7%) with isolated left to right shunts,
percentile weight on first hospitalization, dates of hospital
admissions and discharges, and time between onset of respiratory symptoms and age at which the underlying illness diagnosis was determined. The duration of time between the underlying illness diagnosis and the initial
pneumonia recurrence was calculated.
Confirmation of underlying pulmonary pathologic
characteristics consisted of results from laboratory testing, including sweat chloride testing, pulmonary function
tests with methacholine challenge, a computed tomographic scan of the chest, and/or laryngoscopy and bronchoscopy. Confirmation of cardiac anomalies was based on
findings from an echocardiogram. Most cases of aspiration syndrome were diagnosed clinically. In some patients, however, fluoroscopic feeding studies were performed by occupational therapists to confirm oropharyngeal
incoordination resulting in aspiration. Gastroesophageal reflux was documented either with a barium swallow or esophageal pH manometry.
Quantitative serum immunoglobulins (IgG, IgA, and
IgM) were quantified using a nephelometer analyzer
(Behring Nephelometer Analyzer; Behring Diagnostics Inc,
Newark, NJ). The T and B lymphocytes were assayed using lymphoproliferation studies to assay cell function, and
flow cytometry was used to assess the number of lymphocytes. Human immunodeficiency virus (HIV) antibody was
assayed from serum samples using various enzyme-linked
immunosorbent assay systems (IAF Biochem Detect HIV;
Biochem Pharma, Montreal, Quebec, and MEIA; Abbott
Laboratories Inc, Abbott Park, Ill). Microbiological studies, such as sputum samples and nasopharyngeal swabs, were
obtained in only a subgroup of patients.
including atrial and ventricular septal defects, as well as
patent ductus arteriosus. Six other patients had more
complex cardiac disorders. The mean age at diagnosis
of recurrent pneumonia in children with congenital
heart disease was 1.8 years. The mean age at diagnosis
of recurrent pneumonia in the 19 children with asthma
was 4.5 years.
Airway and pulmonary anomalies were diagnosed
early in life and were found in 18 patients. The mean age
of diagnosis was 4 months (age range, 0 days to 6 months).
Children with tracheoesophageal fistulas formed the largest group in this category with 7 patients. Two patients
each had congenital cystic adenomatoid malformation,
vocal cord paralysis, subglottic stenosis, and tracheomalacia. The 3 remaining patients had an esophageal bronchus, a tracheoesophageal cleft, and tracheal stenosis, respectively. The mean age at diagnosis of recurrent
pneumonia in children with airway and pulmonary
anomalies was 3.5 years.
Associated gastroesophageal reflux was found in 13
patients with recurrent pneumonia. In all patients there
was a notable association between feeding and subsequent respiratory symptoms. All of these children were
neurologically normal on physical examination. The mean
age at diagnosis of recurrent pneumonia in children with
gastroesophageal reflux was 1.4 years.
Children for whom no underlying etiologic diagnosis was identified had growth, development, and
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Table 1. Patients With Underlying Causes
of Recurrent Pneumonia
Underlying Illness
Table 2. Timing of Underlying Illness Diagnosis
Relative to the Number of Pneumonia Episodes
No. (%)
Aspiration syndrome
Immune disorder
Congenital heart disease
Bronchial asthma
Anomalies of the respiratory system
Gastroesophageal reflux
Unknown
114 (47.9)
34 (14.3)
22 (9.2)
19 (8.0)
18 (7.6)
13 (5.4)
18 (7.6)
physical examination findings within reference limits.
The mean age at diagnosis of recurrent pneumonia in
these children was 4.8 years. All were asymptomatic
prior to and after the illness leading to hospitalizations.
Findings from all hospital investigations were within
reference limits.
One hundred seventy-eight patients (80.9%) were
diagnosed with an underlying illness prior to the first episode of pneumonia. Twenty-five patients (11.4%) were
diagnosed during the first episode of pneumonia, and 17
(7.7%) were diagnosed only after recurrence (Table 2).
Aspiration disorders, immune disorders, and congenital
heart disease were underlying illnesses that tended to be
known prior to the first pneumonia. Asthma, respiratory tract anomalies, and gastroesophageal reflux tended
to be diagnosed after the first or recurrent pneumonia
(x2 = 127, P = .001).
Of the 17 underlying illness diagnoses discovered
after pneumonia recurrence, asthma was the most common, occurring in 7 patients, followed by oropharyngeal incoordination leading to aspiration in 4. The remaining causes included gastroesophageal reflux disease
in 3 patients, underlying airway anomalies in 2, and immune disorders in 1.
Prior to their asthma diagnosis, children with asthma
presented with episodes of pneumonia but were otherwise healthy. They underwent extensive laboratory evaluation, including sweat chloride and quantitative serum
immunoglobulin measurements. Growth, development, and physical examination findings were all within
reference limits. These children were clinically diagnosed as having asthma (multiple episodes of partially
reversible airway obstruction) or diagnosed by pulmonary function tests.
Recurrent pneumonia prior to a diagnosis of an underlying aspiration disorder was seen in 4 cases. One patient who presented following recurrent pneumonia was
found to have oropharyngeal incoordination with hypotonia. This patient was diagnosed as having nemaline rod
myopathy after abnormal findings from electromyographic studies. The second patient had a brainstem tumor and presented with recurrent bilateral pneumonia from
silent aspiration; neurological signs and symptoms, including headache, loss of appetite, and weight loss, did not
develop until after the second episode of pneumonia. The
remaining 2 patients had familial dysautonomia (RileyDay syndrome) but were initially diagnosed as having bronchial asthma. One child had a family history of the disease prior to hospitalization with pneumonia.
Underlying Illness
Diagnosed Diagnosed
Diagnosed After First
After
Prior to
Pneumonia Pneumonia
Pneumonia
Episode
Recurrence Total
Aspiration syndrome
Immune disorder
Congenital heart
disease
Bronchial asthma
Anomalies of the
respiratory system
Gastroesophageal
reflux
Total
109
26
22
1
7
0
4
1
0
114
34
22
12
9
0
7
7
2
19
18
0
10
3
13
178
25
17
220
In the group of patients with gastroesophageal reflux disease, all were diagnosed as a result of having a
pneumonia episode. Ten patients were diagnosed before age 1 year during the first episode of pneumonia.
Three patients were diagnosed at age 12 to18 months after recurrent pneumonia.
Two patients with an underlying respiratory tract
anomaly (1 with congenital cystic adenomatoid malformation and 1 with esophageal bronchus) were diagnosed after pneumonia recurrence. Both patients had recurrent pneumonia involving the same lung lobes. Seven
patients (2 with tracheoesophageal fistulas; 1, congenital cystic adenomatoid malformation; 2, subglottic stenoses; 1, tracheomalacia; and 1, bronchomalacia) were
diagnosed during the first episode of pneumonia.
One patient with hypogammaglobulinemia was
diagnosed following pneumonia recurrence. This
patient also presented with other features of immune
disorders, including recurrent otitis media, oral candidiasis, and failure to thrive. Two patients were diagnosed with sickle cell anemia during their first episode
of pneumonia. This was suspected secondary to anemia, race, and/or family history. The remaining 8
patients had known sickle cell anemia prior to pneumonia presentation. Five patients with an underlying
immune disorder presented with pneumonia (3 with
acquired immunodeficiency syndrome, 1 with acute
lymphoblastic leukemia, and 1 with a neuroblastoma).
Of the 3 patients with HIV infection, the diagnosis was
suspected during the initial episode of pneumonia
because of the presence of the classic interstitial pattern on chest radiograph films and multiple etiologic
agents on bronchoalveolar lavage specimens, including Pneumocystis carinii, respiratory syncytial virus,
influenza, parainfluenza, and cytomegalovirus. The
patient with acute lymphoblastic leukemia presented
with pneumonia and an elevated white blood cell
count.
COMMENT
Our study demonstrates that most patients with recurrent pneumonia are known to have an underlying illness at the time of pneumonia recurrence. The most fre-
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quent underlying illness is aspiration pneumonia
secondary to oropharyngeal incoordination, followed by
immune disorders, congenital heart disease, asthma, respiratory system anomalies, gastroesophageal reflux, and
sickle cell anemia.
The remaining patients, however, who presented
with recurrent pneumonia without a known underlying illness diagnosis present an interesting diagnostic
challenge. In more than half, a final diagnosis was
determined. Asthma was the most common illness
diagnosed in this population, followed by disorders
causing aspiration, gastroesophageal reflux, and respiratory tract anomalies. Interestingly, congenital
immune disorders was rarely a diagnosis following
investigations for pneumonia recurrence. In approximately one tenth of our population, a predisposing
factor was not found despite comprehensive evaluation. In these patients, however, follow-up information was incomplete.
A considerable number of children with recurrent
pneumonia in our study had concomitant sickle cell anemia. It has long been recognized that children with homozygous sickle cell anemia are at increased risk for pneumonia relative to other children, even with penicillin
prophylaxis treatment.29-31
In children with recurrent pneumonia, age and
location of pneumonia recurrence may be important
clues in discovering underlying illnesses. In the first
few months of life, structural or functional anomalies
of the airway may present as multiple pneumonias of
the same lung lobe. Before age 18 months, gastroesophageal reflux may contribute to recurrent pneumonia. These illnesses should be confirmed with
barium esophagography and/or continuous pH monitoring in children in this age group presenting with
recurrent pneumonia.32 Bilateral interstitial pneumonias on chest radiograph films and/or the presence of
opportunistic infections were paramount in diagnosing HIV infection as an underlying factor in recurrent
pneumonia. Older children with recurrent pneumonia
were often found to have asthma following extensive
investigation.
Our study design had several limitations. Our
study includes only hospitalized patients. However,
one would suspect that most children with recurrent
pneumonia would ultimately be hospitalized. By using
the International Classification of Diseases, Ninth Revision, Clinical Modification 19 codes for hospital discharge diagnoses of pneumonia to identify children
with recurrent pneumonia, we may be underestimating the true number of patients with this condition.
Other children who would have met clinical criteria
for pneumonia would not have been included once
other diagnoses, such as cystic fibrosis, were made.
Perhaps identifying children by hospital admission
diagnoses or secondary diagnoses would have allowed
a more representative sample.
The radiographic diagnosis of pneumonia in our patients is susceptible to bias.33 Reports describing chest radiograph films could not always differentiate atelectasis
or consolidation. The occurrence of true pneumonia may
have been overestimated.
The retrospective nature of our study restricted diagnoses and the types of investigations performed at the
time the patients were diagnosed with pneumonia. Since
children had not undergone a uniform set of investigations, diagnoses may have been inaccurate or incomplete. Furthermore, our study ascribes a single underlying illness as the cause of recurrent pneumonias,
potentially excluding additional factors or multiple diagnoses in children. The assumption that an underlying
patient illness contributed directly to the recurrence of
pneumonia in our study population is also a weakness
in our study. The severity of underlying illnesses was not
assessed, and the “underlying diagnosis” may have been
coincidental, rather than causal.
To our knowledge, this study represents the largest pediatric series of recurrent pneumonia. Most instances of recurrent pneumonia have a known underlying cause, namely oropharyngeal incoordination
predisposing to aspiration. This underlying cause has
tended to be ignored in previous studies of pediatric recurrent pneumonia.
In most children with recurrent pneumonia, underlying illnesses are known prior to the first episode. In undiagnosed recurrent pneumonia, however, asthma and
gastroesophageal reflux, in particular, should be eliminated in the differential diagnosis.
Accepted for publication June 22, 1999.
Corresponding author: Elaine E. L. Wang,
MD, FRCPC, Clinical and Medical Affairs–Canada,
Pasteur Merieux Connaught, 1755 Steeles Ave W, Toronto,
Ontario,CanadaM2R3T4(e-mail:[email protected]).
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